Amongst eligible patients, age and comorbidity do not predict for dose-limiting toxicity from phase I chemotherapy.
Amongst eligible patients, age and comorbidity do not predict for dose-limiting toxicity from phase I chemotherapy.
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DOI：
10.1007/s00280-009-1084-8
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发表时间：
2010-03
影响因子：
3
通讯作者：
Holen, Kyle D.
中科院分区：
文献类型：
--
作者：
LoConte, Noelle K.;Smith, Maureen;Alberti, Dona;Bozeman, Jeffrey;Cleary, James F.;Setala, Ashley N.;Wodtke, Geoff;Wilding, George;Holen, Kyle D.
在I期化疗临床试验中，临床医生没有明确的预测指标来确定谁更有可能出现剂量限制性毒性（DLT）。由于担心出现毒性反应，许多医疗服务提供者不愿意推荐老年人参加I期试验。本研究的目的是确定与I期研究中DLT发生相关的临床和非临床因素。
如果患者接受了最大耐受剂量（MTD）及以上的治疗则被纳入研究。只有达到MTD的研究才被纳入。收集的数据包括年龄、合并症（老年人累积疾病评分）、入组时的实验室检查结果、身高、体重、体能状态、癌症类型、诊断时间、既往治疗、药物水平、吸烟状况、婚姻状况、平均收入、根据邮政编码确定的高中及以上学历人口百分比以及到I期试验医院的距离。通过双变量分析，然后进行多变量分析，对出现和未出现DLT的患者进行比较。
对24项细胞毒性化疗研究的242份病历进行了回顾，涉及27种不同类型的癌症。在双变量分析中，平均年龄、家庭收入（较高）、体重、体表面积、药物剂量、碱性磷酸酶、血红蛋白和乳酸脱氢酶与DLT显著相关（p<0.05）。老年人累积疾病评分与DLT无关。在多变量分析中，剂量水平（p = 0.004）和到I期试验医院的距离（p = 0.04）仍然是DLT的显著预测因素。年龄不能预测DLT的严重程度。
在I期化疗试验中，年龄和合并症不能预测DLT的发生。这些患者中有许多身体状况非常好，老年人累积疾病评分相对较低，因此合并症的影响可能没有得到充分评估。一些社会和临床因素可能预测DLT的发生。正在计划一项前瞻性研究以证实这些结果。
There are no clear predictors clinicians can use to determine who is more likely to experience dose limiting toxicity (DLT) in phase I chemotherapy clinical trials. Many providers are reluctant to refer older adults to phase I trials because of concerns about the development of toxicity. The goal of this study was to identify clinical and nonclinical factors which were associated with the development of DLT in phase I studies Patients (pts) were included if they were treated at maximally tolerated dose (MTD) and above. Studies were included only if MTD was reached. Data collected included age, comorbidity (Cumulative Illness Rating Score-Geriatrics), labs at enrollment, height, weight, performance status, cancer type, duration of diagnosis, prior treatment, drug level, smoking status, marital status, mean income, percent of population high school educated as determined by ZIP code, and distance to the phase I trial hospital. Those who did and did not have DLT were compared by bivariate and then multivariate analysis. 242 charts were reviewed, from 24 cytotoxic chemotherapy studies, and 27 different types of cancer were represented. On bivariate analysis, mean age, household income (higher), weight, body surface area, dose of drug, alkaline phosphatase, hemoglobin, and LDH were significantly associated with DLT (p<0.05). CIRS-G score was not associated with DLT. In multivariate analysis dose level (p=0.004) and distance from the phase I trial hospital (p=0.04) were still significant predictors of DLT. Age did not predict for severity of DLT. Age and comorbidity did not predict for development of DLT in phase I chemotherapy trials. Many of these pts were very fit, with relatively low CIRS-G scores, so the impact of comorbidity may not have been fully evaluated. Several social and clinical factors may predict for development of DLT. A prospective study is being planned to confirm these results.
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